Virol J:L17或可用于HPV相关宫颈癌的预防和治疗

2017-09-24 MedSci MedSci原创

人乳头状瘤病毒(HPV)是子宫颈癌的主要致病因子,HPV蛋白E6和E7是恶性肿瘤发生及发展的主要病因。因此,抑制病毒E6和E7癌蛋白表达或是宫颈癌治疗的可行策略。本研究旨在评估新型N-苯基苯甲酰胺衍生物3-(2-氯丙基酰胺)-4-甲氧基-N-苯基苯甲酰胺(L17)在体外对HPV16的抗病毒作用,并确定其与子宫颈癌细胞相关的作用机制。通过MTT法检测L17的细胞毒作用。分别通过定量实时逆转录PCR(

人乳头状瘤病毒(HPV)是子宫颈癌的主要致病因子,HPV蛋白E6和E7是恶性肿瘤发生及发展的主要病因。因此,抑制病毒E6和E7癌蛋白表达或是宫颈癌治疗的可行策略。本研究旨在评估新型N-苯基苯甲酰胺衍生物3-(2-氯丙基酰胺)-4-甲氧基-N-苯基苯甲酰胺(L17)在体外对HPV16的抗病毒作用,并确定其与子宫颈癌细胞相关的作用机制。

通过MTT法检测L17的细胞毒作用。分别通过定量实时逆转录PCR(qRT-PCR)和Western blot分析E6和E7致癌基因的mRNA和蛋白水平。通过蛋白质印迹检测p53和Rb蛋白的水平。流式细胞术分析L17对细胞周期的影响。

结果显示,宫颈癌细胞中L17的细胞毒作用大于正常细胞。L17可显著降低HPV16 E6和E7 mRNA和蛋白的表达,部分或是通过增强HPV16 E6和E7 mRNA的降解来实现。此外,由L17诱导的E6和E7的表达降低导致p53和Rb表达的上调,其随后在G0/G1期诱导CaSki细胞停滞。

总之,L17可通过抑制E6和E7癌基因的表达发挥抗病毒活性,且可通过在无毒浓度下诱导G0/G1期细胞停滞来抑制CaSki细胞的增殖,表明L17或是HPV相关子宫颈癌预防和治疗的候选药物。

原始出处:

Fang Han, Yanping Li, et al., 3-(2-Chloropropyl amide)-4-methoxy-N-phenylbenzamide inhibits expression of HPV oncogenes in human cervical cancer cell. Virol J. 2017; 14: 145. Published online 2017 Jul 28. doi: 10.1186/s12985-017-0806-5

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  2. [GetPortalCommentsPageByObjectIdResponse(id=2077367, encodeId=281b20e73678a, content=<a href='/topic/show?id=cb141845040' target=_blank style='color:#2F92EE;'>#Virol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18450, encryptionId=cb141845040, topicName=Virol)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/FGFAawy0kQNXbuvUuLtUVrx5aKhOIkwqJwyxu0QlpLFIDSb1Ht19ptXvYBjuAoNBubibnNF3iazdpico7gJlbBVQg/132, createdBy=edaf2500125, createdName=ms3892185887221420, createdTime=Thu Oct 05 20:52:00 CST 2017, time=2017-10-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=248006, encodeId=51612480063d, content=学习了.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=550d2008262, createdName=luominglian113, createdTime=Wed Sep 27 00:10:00 CST 2017, time=2017-09-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1408063, encodeId=69e1140806389, content=<a href='/topic/show?id=92194628826' target=_blank style='color:#2F92EE;'>#宫颈#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46288, encryptionId=92194628826, topicName=宫颈)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=11102737131, createdName=一闲, createdTime=Tue Sep 26 06:52:00 CST 2017, time=2017-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=247389, encodeId=cdec24e3897c, content=好文章.学习了., beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=60791943465, createdName=1e0f8808m18(暂无匿称), createdTime=Mon Sep 25 00:08:36 CST 2017, time=2017-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=247338, encodeId=a63224e3381a, content=不错的.学习了.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NdqKgfW3nMpOkC3jXxiaW2po0PtglY5ZuVjERqKADW4HyMI8bcZXWlKgH7tEP9ULBoBzuQMibia4pr1s9rQPqLvqQJ/0, createdBy=e8c02060444, createdName=中医痴, createdTime=Sun Sep 24 18:04:43 CST 2017, time=2017-09-24, status=1, ipAttribution=)]
    2017-09-27 luominglian113

    学习了.谢谢分享

    0

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    2017-09-26 一闲
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    2017-09-25 1e0f8808m18(暂无匿称)

    好文章.学习了.

    0

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    2017-09-24 中医痴

    不错的.学习了.谢谢分享!

    0

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前不久,中国宫颈癌预防控制科普项目(以下简称项目)启动会在上海举行。中华预防医学会王陇德会长、国家卫生计生委妇幼健康服务司宋莉副司长、上海市卫生计生委王磐石副主任、中华预防医学会副会长兼秘书长杨维中等领导、专家以及媒体约100余人参加了此次会议。